tetano
Editor, Senior Moderator
J Pharmacol Exp Ther. 2012 Sep 17. [Epub ahead of print]
Inhibitory influence of the hexapeptidic sequence SLIGRL on influenza A virus infection in mice.
Betts RJ, Mann TS, Henry PJ.
Source
1 National University of Singapore;
Abstract
Protease-activated receptor-2 (PAR2) is widely expressed in the respiratory tract and is an integral component of the host antimicrobial defence system. The principal aim of this study was to investigate the influence of a PAR2-activating peptide SLIGRL on influenza A virus (IAV)-induced pathogenesis in mice. Intranasal inoculation of BALB/c mice with influenza A/PR/8/34 virus caused time-dependent increases in the number of pulmonary leukocytes (recovered from bronchoalveolar lavage fluid), marked airway histopathology characterised by extensive epithelial cell damage, airway hyperresponsiveness to the bronchoconstrictor methacholine, and elevated levels of inflammatory chemokines (KC, MIP-2) and cytokines (interferon-γ). Interestingly, these IAV-induced effects were dose-dependently attenuated in mice treated with a PAR2 activating peptide SLIGRL at the time of IAV inoculation. However, SLIGRL also inhibited IAV-induced increases in pulmonary leukocytes in PAR2-deficient mice, indicating these antiviral actions were not mediated by PAR2. The potency order obtained for a series of structural analogues of SLIGRL for anti-IAV activity (IGRL > SLIGRL > LSIGRL > f-LIGRL) was also inconsistent with a PAR2-mediated effect. In further mechanistic studies, SLIGRL inhibited IAV-induced propagation in ex vivo perfused segments of trachea from wild-type or PAR2-/- mice, but did not inhibit viral attachment or replication in MDCK cells and chorioallantoic membrane cells which are established hosts for IAV. In summary, SLIGRL protected mice from IAV infection independently of PAR2 and independently of direct inhibition of IAV attachment or replication, potentially through activation of endogenous antiviral pathways within the mouse respiratory tract.
PMID:
22988062
[PubMed - as supplied by publisher]
Free full text
http://www.ncbi.nlm.nih.gov/pubmed/22988062
Inhibitory influence of the hexapeptidic sequence SLIGRL on influenza A virus infection in mice.
Betts RJ, Mann TS, Henry PJ.
Source
1 National University of Singapore;
Abstract
Protease-activated receptor-2 (PAR2) is widely expressed in the respiratory tract and is an integral component of the host antimicrobial defence system. The principal aim of this study was to investigate the influence of a PAR2-activating peptide SLIGRL on influenza A virus (IAV)-induced pathogenesis in mice. Intranasal inoculation of BALB/c mice with influenza A/PR/8/34 virus caused time-dependent increases in the number of pulmonary leukocytes (recovered from bronchoalveolar lavage fluid), marked airway histopathology characterised by extensive epithelial cell damage, airway hyperresponsiveness to the bronchoconstrictor methacholine, and elevated levels of inflammatory chemokines (KC, MIP-2) and cytokines (interferon-γ). Interestingly, these IAV-induced effects were dose-dependently attenuated in mice treated with a PAR2 activating peptide SLIGRL at the time of IAV inoculation. However, SLIGRL also inhibited IAV-induced increases in pulmonary leukocytes in PAR2-deficient mice, indicating these antiviral actions were not mediated by PAR2. The potency order obtained for a series of structural analogues of SLIGRL for anti-IAV activity (IGRL > SLIGRL > LSIGRL > f-LIGRL) was also inconsistent with a PAR2-mediated effect. In further mechanistic studies, SLIGRL inhibited IAV-induced propagation in ex vivo perfused segments of trachea from wild-type or PAR2-/- mice, but did not inhibit viral attachment or replication in MDCK cells and chorioallantoic membrane cells which are established hosts for IAV. In summary, SLIGRL protected mice from IAV infection independently of PAR2 and independently of direct inhibition of IAV attachment or replication, potentially through activation of endogenous antiviral pathways within the mouse respiratory tract.
PMID:
22988062
[PubMed - as supplied by publisher]
Free full text
http://www.ncbi.nlm.nih.gov/pubmed/22988062